1. NIH Guidelines Section III - Levels of Review
Level of review
Example of types of research covered
Relevant section(s) of the NIH Guidelines
IBC, RAC review, and NIH Director review and approval
Experiments that compromise the control of disease agents in medicine through deliberate transfer of a drug resistance trait
III-A
IBC approval and NIH review for containment determinations
Experiment involving the cloning of toxin molecules with LD50 of less than 100 nanograms per kilogram of body weight
III-B
IBC and IRB approval and NIH review before research participant enrollment
Experiments involving the deliberate transfer of recombinant or synthetic nucleic acid molecules into a human research participant
III-C
IBC approval before initiation
Creating stable germline alterations of an animal’s genome, or testing viable recombinant or synthetically modified microorganisms on whole animals, where BL-2 containment or greater is necessary
III-D
IBC notice at initiation
Creating stable germline alterations of rodents by introduction of recombinant or synthetic nucleic acid molecules when these experiments require only BL-1 containment
III-E
Exempt from the NIH Guidelines. IBC registration not required if experiment not covered by Sections III-A, III-B, or III-C
Purchase or transfer of transgenic rodents
III-F

2. Section III-A
Experiments Require IBC Approval, RAC Review and NIH Director Approval Before Initiation
“Major Action”
The deliberate transfer of a drug resistance trait to microorganisms that are not known to acquire the trait naturally, if such acquisition could compromise the use of the drug to control disease agents in humans, veterinary medicine, or agriculture

3. Section III-A

4. Section III-B
Experiments Require NIH OSP and IBC Approval Before Initiation
III-B-1: Experiments involving the cloning of toxin molecules with LD50 of less than 100 nanograms per kilogram body weight
III-B-2: Experiments that have been approved (under Section III-A-1-a) as Major Actions under the NIH Guidelines

5. Section III-C
Experiments Require IBC Approval and IRB Approval (and RAC Review as applicable) Before Initiation
Human gene transfer - deliberate transfer into human research participants of either:
Recombinant nucleic acid molecules, or DNA or RNA derived from recombinant nucleic acid molecules, or
Synthetic nucleic acid molecules, or DNA or RNA derived from synthetic nucleic acid molecules, that meet any one of the following criteria:

6. Section III-C Contain more than 100 nucleotides; or
Possess biological properties that enable integration into the genome (e.g., cis elements involved in integration); or
Have the potential to replicate in a cell; or
Can be translated or transcribed.

7. Section III-D-1 Experiments IBC Require Approval Before Initiation
Experiments Using Risk Group 2, Risk Group 3, Risk Group 4, or Restricted Agents as Host-Vector Systems
Before work begins: submit protocol for IBC review. Must receive approval before work can begin.

8. Section III-D-2 Experiments Require IBC Approval Before Initiation
Experiments in Which DNA From Risk Group 2, Risk Group 3, Risk Group 4, or Restricted Agents is Cloned into Nonpathogenic Prokaryotic or Lower Eukaryotic Host-Vector Systems

9. Section III-D-3 Experiments Require IBC Approval Before Initiation
Experiments Involving the Use of Infectious DNA or RNA Viruses or Defective DNA or RNA Viruses in the Presence of Helper Virus in Tissue Culture Systems

10. Section III-D-4: Experiments Involving Whole Animals
Includes experiments in which:
The animal’s genome has been altered by stable introduction of recombinant or synthetic nucleic acids into germline (transgenic animals)
Viable recombinant or synthetic nucleic acid molecule-modified microorganisms are tested on whole animals
The definition of “animal” is much broader than the IACUC definition of animal. Example organisms that would fall under this category include Drosophila (always), C. elegans, mosquitoes.

11. Section III-D-5: Experiments Involving Whole Plants
Includes experiments in which:
Plants are genetically engineered by recombinant or synthetic nucleic acid molecule methods
Plants are used with recombinant or synthetic nucleic acid molecule containing insects
Generally BL2-P through BL4-P, depending on risk

12. Section III-D-6: Experiments Involving More Than 10L of Culture
Also See Appendix K
The AGGREGATE volume has to be >10 L. A 9.9 L volume is OK, even if there are multiple volumes of this size contained separately in the system.

13. Section III-D-7 Experiments Involving Influenza Viruses
Generated by recombinant or synthetic methods (e.g., reverse genetics of chimeric viruses with reassorted segments, introduction of specific mutations) shall be conducted at the biosafety level containment corresponding to the risk group of the virus that was the source of the majority of segments in the recombinant virus
Experiments with influenza viruses containing genes or segments from H1N1 (1918 H1N1), human H2N2 ( ) and highly pathogenic avian influenza H5N1 strains within the Goose/Guangdong/96-like H5 lineage (HPAI H5N1) shall be conducted at BL3 enhanced containment

14. Section III-E
Experiments Require IBC Notice Simultaneous with Initiation
E-1 Experiments Involving the Formation of Recombinant or Synthetic Nucleic Acid Molecules Containing No More than Two-Thirds of the Genome of any Eukaryotic Virus
E-2 Experiments Involving Whole Plants
E-3 Experiments Involving Transgenic rodents
Also - Experiments not included in III-A through III-D or III-F that can be conducted at BSL1
This category of works till needs IBC review & approval but work can begin before review starts. By default, if work doesn’t fall under any other category IIIA-IIID or IIIF, then it would fall here (this is the “catch all” category)

15. Section III-E-3
Experiments Involving the Generation of Transgenic Rodents
Experiments in which:
Rodent’s genome has been altered by stable introduction of recombinant or synthetic nucleic acid molecules into germline
BL1 containment is appropriate

16. Section III-F: Exempt Experiments
Registration with the Institutional Biosafety Committee is not required (although many institutions may require this by policy)

17. Section III-F-1: Exempt Experiments
Synthetic nucleic acids that:
can neither replicate nor generate nucleic acids that can replicate in any living cell (e.g., oligonucleotides or other synthetic nucleic acids that do not contain an origin of replication or contain elements known to interact with either DNA or RNA polymerase), and
are not designed to integrate into DNA, and
do not produce a toxin that is lethal for vertebrates at an LD50 of less than 100 nanograms per kilogram body weight.

18. Section III-F-1: Exempt Experiments
Note: If a synthetic nucleic acid is deliberately transferred into one or more human research participants and meets the amended criteria of Section III-C, it is not exempt under the NIH Guidelines.

19. Section III-F-2 Exempts the following experiments:
Those that are not in organisms, cells or viruses and that have not been modified or manipulated (e.g., encapsulated into synthetic or natural vehicles) to render them capable of penetrating cellular membranes.
If work not performed in a living sytem (PCR, in vitro, sequencing) would fall under this category and be considered exempt.

20. Section III-F-3
Those that consist entirely of recombinant or synthetic nucleic acid sequence from a single source that exists contemporaneously in nature
But if you combine DNA from 2 plasmids, would be covered by NIH Guidelines

21. Section III-F-4
Those that consist entirely of nucleic acids from a prokaryotic host including its indigenous plasmids or viruses when propagated only in that host (or a closely related strain of the same species), or when transferred to another host by well established physiological means.
If natural processes are used to do the transfer of material = Exempt

22. Section III-F-5
Those that consist entirely of nucleic acids from an eukaryotic host including its chloroplasts, mitochondria, or plasmids (but excluding viruses) when propagated only in that host (or a closely related strain of the same species).
Example: Took DNA from a mouse and put it back in the mouse = exempt

23. Section III-F-6
Those that consist entirely of DNA segments from different species that exchange DNA by known physiological processes, though one or more of the segments may be a synthetic equivalent.
Meaning recombinant DNA molecules that are:
composed entirely of DNA segments from one or more of the organisms within a sublist, and
to be propagated in any of the organisms within the same sublist

24. Section III-F-7
Those genomic DNA molecules that have acquired a transposable element provided the transposable element does not contain any recombinant and/or synthetic DNA

25. Section III-F-8
Those that do not present a significant risk to health or the environment as determined by the NIH Director, with the advice of the RAC, and following appropriate notice and opportunity for public comment.
See Appendix C, Exemptions under Section III-F-8